Opioid-containing oral pharmaceutical compositions and methods

• US 8,362,029 B2
• Filed: 12/31/2009
• Issued: 01/29/2013
• Est. Priority Date: 12/31/2008
• Status: Expired due to Fees

• Current Assignee: Upsher-Smith Laboratories, LLC (SAWAI GROUP HOLDINGS Co., Ltd.)
• Original Assignee: Upsher-Smith Laboratories Incorporated (SAWAI GROUP HOLDINGS Co., Ltd.)
• Inventors: Evenstad, Kenneth L., Wertz, Christian F., Jensen, James S., O'Neill, Victoria Ann, Berge, Stephen M.
• Primary Examiner(s): Lundgren, Jeffrey S.
• Assistant Examiner(s): LEE, WILLIAM Y
• Application Number:
  US13/142,784
• Publication Number:
  US 20110275658A1
• Time in Patent Office: 1,125 Days
• Field of Search: None
• US Class Current: 514/282
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/10 Sulfides; Sulfoxides; Sulfones
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/439 the ring forming part of a bridged ring system, e.g. quinuclidine 8-azabicyclo [3.2.1] octanes A61K31/46
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids

Abstract

The present invention provides sustained-release oral pharmaceutical compositions and methods of use. The sustained-release oral pharmaceutical compositions include an opioid (including salts thereof) and a salt of a non-steroidal anti-inflammatory drug (NSAID).

Claims

1. A sustained-release oral pharmaceutical composition comprising within a single dosage form:

a hydrophilic matrix;

a therapeutically effective amount of an opioid; and

a salt of a non-steroidal anti-inflammatory drug (NSAID);

wherein the opioid and the salt of an NSAID are within the hydrophilic matrix; and

wherein the composition exhibits a release profile with respect to the opioid, wherein the release profile comprises a substantial portion that is representative of zero-order release kinetics under in vitro conditions as a result of dissolution of the hydrophilic matrix.

2. The composition of claim 1 wherein the opioid has analgesic properties.

3. The composition of claim 1 wherein the opioid comprises a tertiary amine.

4. The composition of claim 3 wherein the opioid comprises a ring nitrogen that is a tertiary amine.

5. The composition of claim 1 wherein the opioid is selected from the group consisting of morphine, codeine, hydromorphone, hydrocodone, oxycodone, oxymorphone, desomorphine, diacetylmorphine, buprenorphine, dihydrocodeine, nicomorphine, benzylmorphine, fentanyl, methadone, tramadol, propoxyphene, levorphanol, meperidine, and combinations thereof.

6. The composition of claim 1 wherein the opioid is a salt comprising a hydrochloride, a bitartrate, an acetate, a naphthylate, a tosylate, a mesylate, a besylate, a succinate, a palmitate, a stearate, an oleate, a pamoate, a laurate, a valerate, a hydrobromide, a sulfate, a methane sulfonate, a tartrate, a citrate, a maleate, or a combination of the foregoing.

7. The composition of claim 1 wherein the NSAID salt is selected from the group consisting of a salicylate derivative, a 2-aryl propionic acid derivative, a pyrazolidine derivative, an N-arylanthranilic acid derivative, an oxicam derivative, an arylalkanoic acid, an indole derivative, and combinations thereof.

8. The composition of claim 1 wherein the opioid is present in a pain-reducing amount.

9. The composition of claim 1 wherein the NSAID salt is present in an amount effective to provide zero-order release kinetics under in vitro conditions.

10. The composition of claim 1 wherein the single dosage form is a tablet form.

11. The composition of claim 1 wherein the hydrophilic matrix comprises at least one hydrophilic polymeric compound selected from the group consisting of a gum, a cellulose ether, an acrylic resin, a polyvinyl pyrrolidone, a protein-derived compound, and combinations thereof.

21. The composition of claim 1 wherein the dosage form comprises:

an uncoated sustained-release core including the hydrophilic matrix; and

an outer coating over the matrix.

22. The composition of claim 21 wherein the outer coating is substantially uniform.

12. A sustained-release oral pharmaceutical composition comprising within a single dosage form:

a hydrophilic matrix comprising a hydroxypropyl methylcellulose;

a therapeutically effective amount of an opioid selected from the group consisting of hydrocodone, a salt thereof, and combinations thereof; and

a salt of a non-steroidal anti-inflammatory drug (NSAID) selected from the group consisting of a salt of naproxen, and combinations thereof;

wherein the opioid and the salt of an NSAID are within the hydrophilic matrix; and

wherein the composition exhibits a release profile with respect to the opioid, wherein the release profile comprises a substantial portion that is representative of zero-order release kinetics under in vitro conditions as a result of dissolution of the hydrophilic matrix.

13. The composition of claim 12 further comprising a pharmaceutically acceptable anionic surfactant.

14. The composition of claim 13 wherein the pharmaceutically acceptable anionic surfactant is present in a release-modifying amount.

15. The composition of claim 13 wherein the pharmaceutically acceptable anionic surfactant is docusate sodium.

16. The composition of claim 12 wherein the NSAID salt is present in an amount effective to provide zero-order release kinetics under in vitro conditions.

17. The composition of claim 12 wherein the single dosage form is a tablet form.

23. The composition of claim 12 wherein the dosage form comprises:

an uncoated sustained-release core including the hydrophilic matrix; and

an outer coating over the matrix.

24. The composition of claim 23 wherein the outer coating is substantially uniform.

18. A sustained-release oral pharmaceutical composition comprising

within a single dosage form:

a hydrophilic matrix;

a therapeutically effective amount of an opioid;

a salt of a non-steroidal anti-inflammatory drug (NSAID); and

a pharmaceutically acceptable anionic surfactant;

wherein the opioid, the salt of an NSAID, and the anionic surfactant are within the hydrophilic matrix; and

wherein the opioid is released as a result of dissolution of the hydrophilic matrix.

19. The composition of claim 18 which exhibits a release profile with respect to the opioid comprising a substantial portion that is representative of zero-order release kinetics under in vitro conditions as a result of dissolution of the hydrophilic matrix.

20. The composition of claim 18 wherein the pharmaceutically acceptable anionic surfactant is present in a release-modifying amount.

25. The composition of claim 18 wherein the dosage form comprises:

an uncoated sustained-release core including the hydrophilic matrix; and

an outer coating over the matrix.

26. The composition of claim 25 wherein the outer coating is substantially uniform.